Wound healing/plastic surgerySide-to-side nerve bridges reduce muscle atrophy after peripheral nerve injury in a rodent model
Introduction
There is an enormous clinical need for improved outcomes after nerve repair in the setting of trauma, fractures, and nerve plexus injuries [1], [2]. Axonal regeneration is a slow process occurring at approximately 1 mm/d [3]. In the case of proximal peripheral nerve injury, the process of regeneration and reinnervation may take years because of the large distance from the point of injury to the site of distal muscle innervation. During this time, the denervated end organs undergo histologic changes that are consistent with muscle atrophy and infiltration of fibrous tissue [3]. These changes lead to impaired physiological function, resulting in long-term disabilities.
Currently, the gold standard for repairing nerve gaps are autologous nerve grafts. Unfortunately, this technique is associated with significant donor site morbidity, neuromas, and variable ability to prevent muscle atrophy at the end organ. One strategy to minimize donor site morbidity is to use synthetic conduits, which can bridge short gaps. Present research aims to increase the gap length that can be successfully bridged by using growth factors, stem cells, or a combination of the two along with synthetic conduits [4]. Preliminary results using these enhanced conduits are promising, however, distant muscle atrophy remains a problem.
Another strategy to minimize muscle atrophy is the coaptation of an injured nerve to a healthy donor nerve in an end-to-side fashion. This technique can reinnervate a paralyzed muscle and minimize muscle atrophy. The use of end-to-side neurorrhaphy has resulted in improvements in muscle mass through motor neuron collateral sprouting via an epineurial window on the healthy donor nerve to the recipient nerve [5], [6], [7]. As an extension of end-to-side nerve coaptation, we propose that connecting a healthy donor nerve to an injured nerve in a side-side fashion via a synthetic conduit will result in similar improvements in muscle mass. In the setting of a proximally injured and repaired peripheral nerve, these side-to-side connections may function to babysit the muscle during which time the damaged nerve is regenerating. We have therefore designed the present study to combine the traditional end-to-end neurorrhaphy with a distal side-to-side synthetic nerve bridge. We hypothesize that connecting a healthy nerve to a proximally damaged nerve via a distal side-to-side nerve bridge through epineurial windows will reduce muscle atrophy during which time the damaged nerve is regenerating. This combined method is projected to reduce muscle atrophy and improve muscle function.
Section snippets
Surgical procedures
All procedures were approved by the University of Utah Institutional Animal Care and Use Committee (09-09017). A total of 28 male Sprague-Dawley rats weighing 350–400 g were used for this study. The rats were anesthetized using ketamine 50 mg/kg and xylazine 5 mg/kg by intramuscular injection in the contralateral hind limb [6]. The surgical area was shaved and prepared with betadine. A longitudinal incision was then made in the posterior distal thigh of the hind limb, separating the natural
Walking track analysis
All four groups had a decrease in the tibial nerve functional index after surgery and a steady improvement over time. By week 11, both groups 3 and 4 showed a greater magnitude of improvement over groups 1 and 2 (P < 0.05) (Fig. 3A). There were no group differences for the sciatic and peroneal functional index (Fig. 3B and C).
Gastrocnemius muscle mass and nuclear density
Grossly group 3's gastrocnemius muscles exhibited the least amount of atrophy relative to the contralateral untreated muscle when compared with the other groups (Fig. 4).
Discussion
This study demonstrated that the use of a distal side-to-side nerve bridge concomitant with repair of a proximally transected nerve results in decreased gastrocnemius muscle atrophy. Groups 3 and 4, both of which had a nerve bridge, showed greater functional improvements in gait by week 11 compared with the two groups without the nerve bridge. This was true, although group 4 did not have the transected nerve repaired. The use of the side-to-side bridge combined with repair of the transected
Conclusions
The repair of peripheral nerve injuries is a major clinical obstacle, as nerves regenerate at a slow rate resulting in muscle atrophy and loss of function. The present study demonstrates that a distal side-to-side nerve bridge in conjunction with repair of a proximally transected nerve in a rat model results in superior outcomes in terms of improved functional recovery and reduced muscle atrophy. This new surgical approach could greatly improve patient outcomes after peripheral nerve injury
Acknowledgment
The authors would like to thank Jessica Kohan for her assistance with image analysis.
Dr Shea assisted in the study design, data collection, analysis, interpretation, and manuscript preparation. Mr Garlick assisted with surgical procedures, data collection, analysis, interpretation, and manuscript preparation. Dr Salama collected and analyzed all histologic data and assisted in manuscript preparation. Dr Mendenhall assisted in study design, surgical procedures, data collection, and manuscript
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